Knee osteoarthritis (OA) is a leading cause of chronic disability in the elderly. The natural rate of progression or worsening of knee OA varies; the reasons for this are poorly understood. The influence of impairments in the local, joint-organ-level environment on CA progression rate or on patient-centered physical functioning has received little attention. Whether such impairments develop before or after CA onset, they may contribute to subsequent CIA progression and/or functional decline. Meniscal tears and malalignment are local impairments which are present in a subset of patients with mild-moderate CA and adversely affect load distribution. The effect of medial meniscal tears may be greatest when coupled with various malalignment, which further stresses the medial compartment. Another key element of the local environment is the functional capacity of the cartilage itself, i.e. its ability to withstand and transmit load. At present, there is no established method to assess this suitable for application in large studies. Our primary goal is to examine the relationship of meniscal tears and malalignment with tibiofemoral progression and with functional status decline in a cohort of 300 patients with knee CIA. Secondarily, we will examine the impact of malalignment, laxity, muscle weakness and proprioception impairment on long-term (0-7 year) outcome. We also propose to measure cartilage deformation after exercise (which may be an in vivo measure of the functional capacity of cartilage) in a pilot study involving a subset of the cohort. An MAMDC-funded, longitudinal, natural history study of knee OA with radiographic and functional status outcomes is ongoing at our institution, the study of Mechanical Factors in Arthritis of the Knee (MAK), in which time 0, 1.5 (completed) and 3 year (ongoing) evaluations of alignment, laxity, proprioception and strength in 300 subjects are funded. The project proposed here builds upon the infrastructure and results of this study. Support to evaluate the MAK cohort at 5 and 7 years (on the MAK timeline) is sought. The proposed study will provide much needed information regarding potential determinants of the natural outcome of knee OA and will help to identify the local, organ-level factors which should ultimately become the target of intervention, based upon their link to disease progression and/or their link to declining functional status.